“Genetic and clinical findings in an ethnically diverse retinitis pigmentosa cohort associated with pathogenic variants in EYS”

Background and objectives: The EYS gene is an important cause of autosomal recessive retinitis pigmentosa (arRP). The objective of this study is to report on novel pathogenic variants in EYS and the range of associated phenotypes. / Subjects and methods: This retrospective case series at a tertiary referral centre for inherited retinal diseases describes patients with an IRD and at least two variants in the EYS gene. Phenotyping included multimodal retinal imaging; genotyping molecular genetic analysis using targeted next generation sequencing. Sanger sequencing verification and analysis of novel variants using in silico approaches to determine their predicted pathogenicity. / Results: Eight male and four female patients were included. Age at onset ranged from 11 to 62 years with variable symptom presentation; ten patients showed classical features of retinitis pigmentosa, albeit with great variation in disease severity and extent. Two patients had atypical phenotypes: one with localised inferior sector pigmentation and a mild RP phenotype with changes predominantly at the posterior pole. Eighteen variants in EYS were identified, located across the gene: six were novel. Eight variants were missense, two altered splicing, one was a whole exon duplication and the remainder were predicted to result in premature truncation of the protein. / Conclusion: The marked variability in severity and age of onset in most patients in this ethnically diverse cohort adds to growing evidence that that mild phenotypes are associated with EYS variants. Similarly, the two atypical cases add to the growing diversity of EYS disease as do the six novel pathogenic variants described

A new measurement of direct CP violation in two pion decays of the neutral kaon

The NA48 experiment at CERN has performed a new measurement of direct CP violation, based on data taken in 1997 by simultaneously collecting K_L and K_S decays into pi0pi0 and pi+pi-. The result for the CP violating parameter Re(epsilon'/epsilon) is (18.5 +/- 4.5(stat)} +/- 5.8 (syst))x10^{-4}.Comment: 18 pages, 6 figure

Measurement of the branching ratios of the decays Xi0 --> Sigma+ e- nubar and anti-Xi0 --> anti-Sigma+ e+ nu

From 56 days of data taking in 2002, the NA48/1 experiment observed 6316 Xi0 --> Sigma+ e- nubar candidates (with the subsequent Sigma+ --> p pi0 decay) and 555 anti-Xi0 --> anti-Sigma+ e+ nu candidates with background contamination of 215+-44 and 136+-8 events, respectively. From these samples, the branching ratios BR(Xi0 --> Sigma+ e- nubar)= (2.51+-0.03stat+-0.09syst)E(-4) and BR(anti-Xi0 --> anti-Sigma+ e+ nu)= (2.55+-0.14stat+-0.10syst)E(-4) were measured allowing the determination of the CKM matrix element |Vus| = 0.209+0.023-0.028. Using the Particle Data Group average for |Vus| obtained in semileptonic kaon decays, we measured the ratio g1/f1 = 1.20+-0.05 of the axial-vector to vector form factors.Comment: 16 pages, 11 figures Submitted to Phys.Lett.

Recent NA48/2 and NA62 results

The NA48/2 Collaboration at CERN has accumulated and analysed unprecedented statistics of rare kaon decays in the $K_{e4}$ modes: $K_{e4}(+-)$ ($K^\pm \to \pi^+ \pi^- e^\pm \nu$) and $K_{e4}(00)$ ($K^\pm \to \pi^0 \pi^0 e^\pm \nu$) with nearly one percent background contamination. It leads to the improved measurement of branching fractions and detailed form factor studies. New final results from the analysis of 381 $K^\pm \to \pi^\pm \gamma \gamma$ rare decay candidates collected by the NA48/2 and NA62 experiments at CERN are presented. The results include a decay rate measurement and fits to Chiral Perturbation Theory (ChPT) description.Comment: Prepared for the Proceedings of "Moriond QCD and High Energy Interactions. March 22-29 2014." conferenc

ChPT tests at the NA48 and NA62 experiments at CERN

The NA48/2 Collaboration at CERN has accumulated unprecedented statistics of rare kaon decays in the Ke4 modes: Ke4(+-) ($K^\pm \to \pi^+ \pi^- e^\pm \nu$) and Ke4(00) ($K^\pm \to \pi^0 \pi^0 e^\pm \nu$) with nearly one percent background contamination. The detailed study of form factors and branching rates, based on these data, has been completed recently. The results brings new inputs to low energy strong interactions description and tests of Chiral Perturbation Theory (ChPT) and lattice QCD calculations. In particular, new data support the ChPT prediction for a cusp in the $\pi^0\pi^0$ invariant mass spectrum at the two charged pions threshold for Ke4(00) decay. New final results from an analysis of about 400 $K^\pm \to \pi^\pm \gamma \gamma$ rare decay candidates collected by the NA48/2 and NA62 experiments at CERN during low intensity runs with minimum bias trigger configurations are presented. The results include a model-independent decay rate measurement and fits to ChPT description.Comment: XIIth International Conference on Heavy Quarks and Leptons 2014, Mainz, German

Space charge in ionization detectors and the NA48 electromagnetic calorimeter

The subject of space charge due to positive ions slowly moving in parallel plate ionization chambers is considered. A model for the degradation of the detector response is developed, with particular emphasis on electromagnetic calorimeters. The topics discussed include: (a) the stationary and (b) the time dependent cases; (c) the limit of very large space charge; (d) the electric field dependence of the electron drift velocity; (e) the effect of longitudinal development of showers; (f) the behavior of the average reductions of response and (g) the non-uniformity of response for different positions of the shower axis inside the cell defined by the electrodes. The NA48 calorimeter is used as application and for comparison of results

Overview of the Proton-coupled MCT (SLC16A) Family of Transporters: Characterization, Function and Role in the Transport of the Drug of Abuse γ-Hydroxybutyric Acid

The transport of monocarboxylates, such as lactate and pyruvate, is mediated by the SLC16A family of proton-linked membrane transport proteins known as monocarboxylate transporters (MCTs). Fourteen MCT-related genes have been identified in mammals and of these seven MCTs have been functionally characterized. Despite their sequence homology, only MCT1–4 have been demonstrated to be proton-dependent transporters of monocarboxylic acids. MCT6, MCT8 and MCT10 have been demonstrated to transport diuretics, thyroid hormones and aromatic amino acids, respectively. MCT1–4 vary in their regulation, tissue distribution and substrate/inhibitor specificity with MCT1 being the most extensively characterized isoform. Emerging evidence suggests that in addition to endogenous substrates, MCTs are involved in the transport of pharmaceutical agents, including γ-hydroxybuytrate (GHB), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), salicylic acid, and bumetanide. MCTs are expressed in a wide range of tissues including the liver, intestine, kidney and brain, and as such they have the potential to impact a number of processes contributing to the disposition of xenobiotic substrates. GHB has been extensively studied as a pharmaceutical substrate of MCTs; the renal clearance of GHB is dose-dependent with saturation of MCT-mediated reabsorption at high doses. Concomitant administration of GHB and l-lactate to rats results in an approximately two-fold increase in GHB renal clearance suggesting that inhibition of MCT1-mediated reabsorption of GHB may be an effective strategy for increasing renal and total GHB elimination in overdose situations. Further studies are required to more clearly define the role of MCTs on drug disposition and the potential for MCT-mediated detoxification strategies in GHB overdose

A measurement of the transverse polarization of Lambda-hyperons produced in inelastic pN-reactions at 450 GeV proton energy

A study of the polarization of Λ hyperons produced in inelastic pN reactions induced by the 450 GeV proton beam from the CERN SPS has been performed with the NA48 detector. The Λ hyperons were detected at a fixed angle of 4.2 mrad in the momentum range from 50 GeV/c to 200 GeV/c. The polarization changes from −0.053 ± 0.034 to −0.298 ± 0.074 for a transverse momentum range of the Λ between 0.28 GeV/c and 0.86 GeV/c. The antiΛ polarization is consistent with zero